JPH07309753A - Fatty acid derivative and medicine containing it - Google Patents
Fatty acid derivative and medicine containing itInfo
- Publication number
- JPH07309753A JPH07309753A JP7037258A JP3725895A JPH07309753A JP H07309753 A JPH07309753 A JP H07309753A JP 7037258 A JP7037258 A JP 7037258A JP 3725895 A JP3725895 A JP 3725895A JP H07309753 A JPH07309753 A JP H07309753A
- Authority
- JP
- Japan
- Prior art keywords
- ascorbyl
- linolenic acid
- gamma linolenic
- acid
- dihomo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims description 12
- 150000004665 fatty acids Chemical class 0.000 title description 9
- 235000014113 dietary fatty acids Nutrition 0.000 title description 6
- 229930195729 fatty acid Natural products 0.000 title description 6
- 239000000194 fatty acid Substances 0.000 title description 6
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 4
- 201000011510 cancer Diseases 0.000 claims abstract description 4
- 239000002537 cosmetic Substances 0.000 claims abstract description 4
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 4
- 235000013305 food Nutrition 0.000 claims abstract description 4
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 4
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 3
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 3
- 206010020772 Hypertension Diseases 0.000 claims abstract description 3
- 239000000047 product Substances 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims abstract 5
- HOBAELRKJCKHQD-UHFFFAOYSA-N (8Z,11Z,14Z)-8,11,14-eicosatrienoic acid Natural products CCCCCC=CCC=CCC=CCCCCCCC(O)=O HOBAELRKJCKHQD-UHFFFAOYSA-N 0.000 claims description 25
- -1 ascorbyl dihomo gamma linolenic acid Chemical compound 0.000 claims description 18
- 235000020664 gamma-linolenic acid Nutrition 0.000 claims description 12
- FLRQOWAOMJMSTP-JJTRIOAGSA-N [(2s)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethyl] (6z,9z,12z)-octadeca-6,9,12-trienoate Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O FLRQOWAOMJMSTP-JJTRIOAGSA-N 0.000 claims description 11
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 claims description 11
- HOBAELRKJCKHQD-QNEBEIHSSA-N dihomo-γ-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCCCC(O)=O HOBAELRKJCKHQD-QNEBEIHSSA-N 0.000 claims description 10
- 235000021298 Dihomo-γ-linolenic acid Nutrition 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 239000002502 liposome Substances 0.000 claims description 5
- 239000000443 aerosol Substances 0.000 claims description 3
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 claims description 3
- 229960002733 gamolenic acid Drugs 0.000 claims description 3
- 210000002345 respiratory system Anatomy 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010014476 Elevated cholesterol Diseases 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims 1
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims 1
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims 1
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 4
- 208000035475 disorder Diseases 0.000 abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 2
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000004520 agglutination Effects 0.000 abstract 1
- 235000012000 cholesterol Nutrition 0.000 abstract 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 25
- 235000010323 ascorbic acid Nutrition 0.000 description 13
- 239000011668 ascorbic acid Substances 0.000 description 13
- 229960005070 ascorbic acid Drugs 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001486234 Sciota Species 0.000 description 3
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- MAAVGFJWXMUHAT-QNEBEIHSSA-N (6z,9z,12z)-octadeca-6,9,12-trienoyl chloride Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(Cl)=O MAAVGFJWXMUHAT-QNEBEIHSSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102220547770 Inducible T-cell costimulator_A23L_mutation Human genes 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- DMPKFTRGFIFWKY-ZAZQSFEBSA-N docosahexaenoyl-L-ascorbic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O DMPKFTRGFIFWKY-ZAZQSFEBSA-N 0.000 description 1
- 235000007677 docosahexaenoyl-L-ascorbic acid Nutrition 0.000 description 1
- 239000011588 docosahexaenoyl-L-ascorbic acid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Birds (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Furan Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は脂肪酸のアスコルビン酸
（ビタミンＣ) 誘導体に関する。FIELD OF THE INVENTION This invention relates to ascorbic acid (vitamin C) derivatives of fatty acids.
【０００２】[0002]
【従来の技術】脂肪酸のアスコルビン酸誘導体（１）BACKGROUND OF THE INVENTION Ascorbic acid derivative of fatty acid (1)
【化１】 [Chemical 1]
【０００３】（式中Ｒは脂肪酸鎖であり、そしてＲ1 は
ＨまたはＲである）は知られている。すなわち、 Kanek
o らは Arch. Biochem. Biophys.304 No.1, 176-180,(1
993)において、アスコルビン酸の６−Ｏ−パルミトイ
ル、６−Ｏ−ステアロイルおよび2,６−Ｏ−ジパルミト
イルエステルおよび２−Ｏ−オクタデシルエーテル誘導
体により示される、ヒト細胞培養物におけるリノール酸
ヒドロペルオキシドの細胞毒性に対する保護作用につい
て報告している。同様にアスコルビルドコサヘキサエノ
エートの製造も記載されている。Where R is a fatty acid chain and R 1 is H or R are known. That is, Kanek
o et al. Arch. Biochem. Biophys. 304 No. 1, 176-180, (1
993), of 6-O-palmitoyl, 6-O-stearoyl and 2,6-O-dipalmitoyl esters of ascorbic acid and 2-O-octadecyl ether derivatives of linoleic acid hydroperoxides in human cell cultures. The protective effect against cytotoxicity is reported. Also described is the production of ascorbyl docosahexaenoate.
【０００４】さらに、不飽和脂肪酸はホスホリル化モノ
−またはジ−脂肪族アシルグリセリドと一緒に用いられ
た、場合によりパルミテートまたはステアレートの形態
をしていてもよいアスコルビン酸により、大気による酸
化から保護された(Cloughley, 英国特許出願 UK 92 133
22.2に基づくヨーロッパ特許出願 EPA 93304827.4 参
照）。Furthermore, unsaturated fatty acids are protected from atmospheric oxidation by ascorbic acid used together with phosphorylated mono- or di-aliphatic acylglycerides, optionally in the form of palmitate or stearate. (Cloughley, UK patent application UK 92 133
See European patent application EPA 93304827.4 based on 22.2).
【０００５】また、ガンマリノレン酸（以下、ＧＬＡと
略記する）またはジホモガンマリノレン酸（以下、ＤＧ
ＬＡと略記する）とアスコルビン酸とを同時に投与する
着想は本発明者らによるこれまでの多数の出願、例えば
ヨーロッパ特許出願 EPA 0 019 423および EPA 0 085 5
79中に公表されている。Further, gamma linolenic acid (hereinafter abbreviated as GLA) or dihomo gamma linolenic acid (hereinafter DG)
(Abbreviated as LA) and ascorbic acid are co-administered in a number of previous applications by the inventors, for example European patent applications EPA 0 019 423 and EPA 0 085 5.
Published in 79.
【０００６】[0006]
【発明が解決しようとする課題】しかしながら、 Kaneb
o の特開昭62‐081307号公報には化粧品組成物中におけ
るアスコルビン酸のＧＬＡエステルが開示されている
が、脂肪酸のアスコルベートエステルには一般的にあま
り注意が払われていなかった。アスコルビン酸はもちろ
ん健康に必須の水溶性ビタミンとしてよく知られてい
る。アスコルビン酸がＤＧＬＡのプロスタグランジンＥ
1（以下、ＰＧＥ1 と略記する）への変換を刺激しうる
という事実はあまり認められていない。ＰＧＥ1は例外
的に広範囲の望ましい作用を有する、生存期間の短い物
質である。このものは血管および気管支および細気管支
を拡張させ、血小板凝集を抑制し、抗炎症作用を及ぼ
し、コレステロールレベルを低下させ、血圧を低下さ
せ、そして抗癌および抗転移作用を含めた他の望ましい
一連の作用を有すると考えられている。[Problems to be Solved by the Invention] However, Kaneb
Japanese Unexamined Patent Publication (Kokai) No. 62-081307 discloses a GLA ester of ascorbic acid in a cosmetic composition, but attention has generally not been paid to an ascorbate ester of a fatty acid. Ascorbic acid is of course well known as a water-soluble vitamin essential for health. Ascorbic acid is DGLA prostaglandin E
The fact that it can stimulate conversion to 1 (hereinafter abbreviated as PGE 1 ) is not well accepted. PGE 1 is a short-lived substance with an exceptionally wide range of desirable effects. It dilates blood vessels and bronchi and bronchioles, suppresses platelet aggregation, exerts anti-inflammatory effects, lowers cholesterol levels, lowers blood pressure, and other desirable series including anti-cancer and anti-metastatic effects. Is considered to have the action of.
【０００７】ＰＧＥ1 の望ましい作用にかんがみ、体内
でのその形成にとって最適の条件が存在する筈である。
このことの保証を求める一つの方法は、ＤＧＬＡまたは
その直接の前駆体ＧＬＡの摂取を増大させることであ
る。もう一つは、ＰＧＥ1 の形成を促進するためのアス
コルビン酸の適切なレベルを提供することである。Given the desired action of PGE 1 , there should be optimal conditions for its formation in the body.
One way to seek assurance of this is to increase the uptake of DGLA or its immediate precursor GLA. Another is to provide adequate levels of ascorbic acid to promote the formation of PGE 1 .
【０００８】[0008]
【課題を解決するための手段】今、ＧＬＡおよびＤＧＬ
Ａを、以下にアスコルビルＧＬＡおよびアスコルビルＤ
ＧＬＡと称するそれらのアスコルビン酸−６−エステル
として投与することが特に有利であることが判明した。
これら化合物は、好適な溶媒例えばジメチルアセトアミ
ド／ジクロロメタン中、本明細書に記載する−10℃から
30℃の間の温度で、鉱酸触媒すなわち塩化水素の存在下
に脂肪酸の酸クロライドまたは無水物を反応させること
により合成できる。これらは多くの状態において薬剤と
して使用でき、そして本発明はかかる状態におけるそれ
らの使用およびその目的のための薬剤の製造における使
用を包含するものである。前記状態には以下のものが包
含される。 （ａ）ＰＧＥ1 が有効で安全な気管支拡張剤かつ抗炎症
剤であり、そして気道の拡張および、今や喘息における
主要因子であると認識される気道の炎症の長期間にわた
る抑制の両方において特に望ましい効果を有する可能性
がある喘息および関連障害、（ｂ）アテローム性動脈硬
化症関連心臓血管障害、および／またはコレステロール
上昇、および／または高血圧、および／または血小板凝
集過剰、（ｃ）リウマチ様関節炎、骨関節炎、皮膚炎お
よびその他の炎症性障害、（ｄ）癌。[Means for Solving the Problems] Now, GLA and DGL
A to Ascorbyl GLA and Ascorbyl D
It has proved to be particularly advantageous to administer them as their ascorbic acid-6-esters called GLA.
These compounds may be prepared in a suitable solvent such as dimethylacetamide / dichloromethane from −10 ° C. as described herein.
It can be synthesized by reacting an acid chloride or anhydride of a fatty acid in the presence of a mineral acid catalyst, ie hydrogen chloride, at a temperature between 30 ° C. They can be used as medicaments in many situations, and the invention covers their use in such situations and in the manufacture of medicaments for that purpose. The above states include the following. (A) PGE 1 is an effective and safe bronchodilator and anti-inflammatory agent, and is particularly desirable both for dilation of the airways and for long-term inhibition of airway inflammation, now recognized to be a major factor in asthma. Asthma and related disorders that may have an effect, (b) atherosclerosis-related cardiovascular disorders, and / or elevated cholesterol, and / or hypertension, and / or hyperplatelet aggregation, (c) rheumatoid arthritis, Osteoarthritis, dermatitis and other inflammatory disorders, (d) cancer.
【０００９】化粧品またはスキンケア製品、およびまた
任意の種類の食品しかし特に栄養補足物も包含される。
アスコルビルＤＧＬＡの特別の価値は、ＰＧＥ1 生合成
にとって直接の基質であるＤＧＬＡ、および基質ＤＧＬ
ＡのＰＧＥ1 への変換を増強でするであろう刺激剤アス
コルベートの両者を同時にかつ正確に同じ場所に提供す
ることである。我々の知る限りでは、化合物アスコルビ
ルＤＧＬＡはこれまでに記載されたことはない。Also included are cosmetic or skin care products, and also foods of any kind, but especially nutritional supplements.
A special value of ascorbyl DGLA is DGLA, which is a direct substrate for PGE 1 biosynthesis, and the substrate DGL.
To provide both the stimulant ascorbate, which would enhance the conversion of A to PGE 1 , simultaneously and exactly in the same place. To our knowledge, the compound Ascorbyl DGLA has never been described.
【００１０】このエステルはカプセル、錠剤、クリー
ム、溶液、乳剤、粉剤、リポソームまたはその他の形態
で一日当り0.１mg〜50ｇ、好ましくは10mg〜10ｇそして
非常に好ましくは 100mg〜５ｇの量で経口、経腸または
非経口的に投与できる。このエステルはまた、この化合
物が 0.001〜50重量％、好ましくは0.１〜20重量％そし
て非常に好ましくは１〜10重量％の濃度で存在するクリ
ーム、軟膏、ローション、乳剤、ペッサリー、坐剤、ス
ティックまたはその他の適切な形態で局所投与すること
もできる。エーロゾル、リポソーム、またはこの薬物の
直接気道への放出を保証するであろうその他の適切な放
出系に同様の濃度を用いることができる。The ester is orally in the form of capsules, tablets, creams, solutions, emulsions, powders, liposomes or other forms in an amount of 0.1 mg to 50 g, preferably 10 mg to 10 g and very preferably 100 mg to 5 g per day, It can be administered enterally or parenterally. The ester is also a cream, ointment, lotion, emulsion, pessary, suppository in which the compound is present in a concentration of 0.001 to 50% by weight, preferably 0.1 to 20% by weight and very preferably 1 to 10% by weight. It can also be topically administered in the form of a stick, or other suitable form. Similar concentrations can be used for aerosols, liposomes, or other suitable release systems that will ensure the release of the drug directly into the respiratory tract.
【００１１】遊離脂肪酸または、ＧＬＡ、ＤＧＬＡおよ
び／または他の抗炎症性脂肪酸であるＥＰＡの１種また
はそれ以上が重要な構成分であるトリグリセリド中に溶
解または分散すべきエステルにとって特に適切な配合
は、好ましくは５重量％またはそれ以上である。特に好
適なトリグリセリドはＧＬＡ、ＤＧＬＡおよびＥＰＡか
ら選択された１，２または３部分を含有するものであ
る。Particularly suitable formulations for free fatty acids or esters to be dissolved or dispersed in triglycerides, in which one or more of GLA, DGLA and / or other anti-inflammatory fatty acids, EPA, are important constituents are: , Preferably 5% by weight or more. Particularly preferred triglycerides are those containing 1, 2 or 3 moieties selected from GLA, DGLA and EPA.
【００１２】[0012]
【実施例】合成例 アスコルビン酸６−（ｚ，ｚ，ｚ−オクタデカ−６，
９，12−トリエノエート）の製造（アスコルビルＧＬ
Ａ；アスコルビルＤＧＬＡは同じ方法で製造できる）
Ｎ，Ｎ−ジメチルアセトアミド（26.5ml）中に塩化水素
ガス（2.0g）を０℃でぶくぶく吹き込んだ。生成するス
ラリーに、ジクロロメタン（13.25ml)中のアスコルビン
酸（9.69g)のスラリーを加え、そしてこの混合物を溶解
が起るまで０℃で攪拌した。この溶液に窒素の下０℃
で、ｚ，ｚ，ｚ−オクタデカ−６，９，12−トリエノイ
ルクロライド（14.8g)を４時間かかって加えそして生成
する混合物を上記温度で18時間そして室温で１時間放置
した。０℃に冷却し、酢酸エチル（200ml)および水（10
0ml)を加え、そしてこの混合物を１時間攪拌した。有機
層をブライン（５×100ml) で洗い、乾燥（Na2SO4) し
そして50℃／10mmHg次に50℃／0.１mm／４時間蒸発させ
て、アスコルビン酸６−［（ｚ，ｚ，ｚ）−オクタデカ
−６，９，12−トリエノエート］（18.25g、88％) を淡
黄色ワックス様物質として得た。EXAMPLES Synthesis Example Ascorbic acid 6- (z, z, z-octadeca-6,6
Production of 9,12-trienoate (Ascorbyl GL
A: Ascorbyl DGLA can be manufactured by the same method)
Hydrogen chloride gas (2.0 g) was bubbled into N, N-dimethylacetamide (26.5 ml) at 0 ° C. To the resulting slurry was added a slurry of ascorbic acid (9.69g) in dichloromethane (13.25ml) and the mixture was stirred at 0 ° C until dissolution occurred. To this solution under nitrogen at 0 ° C
At this point, z, z, z-octadeca-6,9,12-trienoyl chloride (14.8 g) was added over 4 hours and the resulting mixture was left at the above temperature for 18 hours and at room temperature for 1 hour. Cool to 0 ° C., ethyl acetate (200 ml) and water (10
0 ml) was added and the mixture was stirred for 1 hour. The organic layer was washed with brine (5 × 100 ml), dried (Na 2 SO 4 ) and evaporated at 50 ° C./10 mmHg then 50 ° C./0.1 mm / 4 hours to give ascorbic acid 6-[(z, z, z) -Octadeca-6,9,12-trienoate] (18.25 g, 88%) as a pale yellow wax-like substance.
【００１３】用途例 １．そのまま、または適当な付形剤と一緒の、アスコル
ビルＧＬＡまたはアスコルビルＤＧＬＡの50、 100、 25
0、 500または750mgを含有する錠剤。 ２．ＧＬＡ、ＤＧＬＡまたはＥＰＡが富化された遊離脂
肪酸中またはＧＬＡ、ＤＧＬＡまたはＥＰＡから１，２
または３個の部分が選択されたトリグリセリド中に溶解
されたアスコルビルＧＬＡまたはアスコルビルＤＧＬＡ
の50、 100、 250または500mgを含有する軟ゼラチンカプ
セルまたは硬ゼラチンカプセル。 ３．アスコルビルＧＬＡまたはアスコルビルＤＧＬＡを
本明細書中に言及した濃度において経口、経腸または非
経口投与するための乳剤、粉剤、液剤、スラリーまたは
溶液。 Application Example 1. Ascorbyl GLA or ascorbyl DGLA 50, 100, 25 neat or with a suitable excipient
Tablets containing 0, 500 or 750 mg. 2. GLA, DGLA or EPA enriched free fatty acids or from GLA, DGLA or EPA 1,2
Or Ascorbyl GLA or Ascorbyl DGLA with three moieties dissolved in the selected triglyceride
Soft or hard gelatin capsules containing 50, 100, 250 or 500 mg of. 3. An emulsion, powder, solution, slurry or solution for oral, enteral or parenteral administration of ascorbyl GLA or ascorbyl DGLA at the concentrations referred to herein.
【００１４】４．アスコルビルＧＬＡまたはアスコルビ
ルＤＧＬＡを本明細書に言及した濃度において局所投与
するための軟膏、クリーム、ローション、シャンプー、
またはその他の適当な形態物。 ５．アスコルビルＤＧＬＡを経口、局所、非経口または
直接気道に投与するための、燐脂質または糖脂質のいず
れかを用いて作られたリポソーム。 ６．アスコルビルＤＧＬＡを含有するスプレー、懸濁
液、吸入器またはその他の呼吸器放出系。4. Ointments, creams, lotions, shampoos for topical administration of ascorbyl GLA or ascorbyl DGLA at the concentrations referred to herein.
Or any other suitable form. 5. Liposomes made with either phospholipids or glycolipids for oral, topical, parenteral or direct airway administration of ascorbyl DGLA. 6. A spray, suspension, inhaler or other respiratory delivery system containing ascorbyl DGLA.
フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 31/375 ＡＢＸ ＡＣＢ ＡＤＡ ＡＤＮ ＡＤＵ Ａ２３Ｌ 1/302 Ａ６１Ｋ 7/00 Ｈ // Ｃ０７Ｄ 307/62 (72)発明者 デイビッド・フレデリック・ホロビン 英国、イングランド、サリー ジー・ユー １ １ビー・エイ、ギルドホード、ウッド ブリッジ・メドウズ、エフアモル・ハウス （番地なし）、スコシア・ファーマシュー ティカルズ・リミテッド内 (72)発明者 フィリップ・ノウルス 英国、イングランド、カーライル・シー・ エイ３ ０エッチ・エイ、キングスタウ ン・インダストリアル・エステート、キン グスタウン・ブロードウェイ、リサーチ・ アンド・デベロップメント・センター（番 地なし）、スコシア・ファーマシューティ カルズ・リミテッド内 (72)発明者 メハール・シン・マンク 英国、イングランド、カーライル・シー・ エイ３ ０エッチ・エイ、キングスタウ ン・インダストリアル・エステート、キン グスタウン・ブロードウェイ、リサーチ・ アンド・デベロップメント・センター（番 地なし）、スコシア・ファーマシューティ カルズ・リミテッド内Continuation of front page (51) Int.Cl. 6 Identification code Office reference number FI Technical indication location A61K 31/375 ABX ACB ADA ADN ADU A23L 1/302 A61K 7/00 H // C07D 307/62 (72) Invention David Frederick Horobin UK, England, Surrey Gyu You 11 Bee A, Guildhord, Woodbridge Meadows, Ehuamor House (no house number), Scotia Pharmaceuticals Limited (72) Inventor Philip Knowles UK, England, Carlisle Sea A 30 H.A., Kingston Industrial Estate, Kingstown Broadway, Research and Development Center (no address), Scotia Pharmaceuticals Limited ( 72) Inventor Mehar Singh Mang United Kingdom, England, Carlisle Sea A 30 H.A., Kingston Industrial Estate, Kingstown Broadway, Research and Development Center (no address), Scotia Pharmaceuticals・ In Limited
Claims (8)
化症関連心臓血管障害、および／またはコレステロール
上昇、および／または高血圧、および／または血小板凝
集過剰、（ｃ）リウマチ様関節炎、骨関節炎、皮膚炎ま
たはその他の炎症性障害、（ｄ）癌、の治療に有用な、
アスコルビルガンマリノレン酸またはアスコルビルジホ
モガンマリノレン酸を含有する薬剤。1. The following: (a) asthma and related disorders, (b) atherosclerosis-related cardiovascular disorders, and / or elevated cholesterol, and / or hypertension, and / or excessive platelet aggregation, and (c) rheumatism. Useful in the treatment of osteoarthritis, osteoarthritis, dermatitis or other inflammatory disorders, (d) cancer,
A drug containing ascorbyl gamma linolenic acid or ascorbyl dihomo gamma linolenic acid.
スコルビルジホモガンマリノレン酸を一日当り0.１mg〜
50ｇ、好ましくは10mg〜10ｇそして非常に好ましくは10
0mg〜５ｇ投与するために配合した、請求項１記載の薬
剤。2. Alcolvir gamma linolenic acid or ascorbyl dihomo gamma linolenic acid from 0.1 mg per day
50 g, preferably 10 mg to 10 g and very preferably 10
The drug according to claim 1, which is formulated to administer 0 mg to 5 g.
スコルビルジホモガンマリノレン酸を組成物の重量当り
0.001〜50％、好ましくは0.１〜20％そして非常に好ま
しくは１〜10％の濃度で配合した、請求項１記載の薬
剤。3. Ascorbyl gamma linolenic acid or ascorbyl dihomo gamma linolenic acid per weight of composition.
A medicament according to claim 1 formulated in a concentration of 0.001 to 50%, preferably 0.1 to 20% and very preferably 1 to 10%.
スコルビルジホモガンマリノレン酸を呼吸管に放出する
ための懸濁液、スプレー、エーロゾル、リポソームまた
はその他の形態物に配合した、喘息および関連障害に関
連した請求項１，２または３記載の薬剤。4. A method for asthma and related disorders formulated in a suspension, spray, aerosol, liposome or other form for releasing ascorbyl gamma linolenic acid or ascorbyl dihomo gamma linolenic acid into the respiratory tract. The drug according to 1, 2, or 3.
スコルビルジホモガンマリノレン酸を、遊離酸またはト
リグリセリドの形態のガンマリノレン酸、ジホモガンマ
リノレン酸またはエイコサペンタエン酸の５重量％また
はそれ以上を含有する油状物と混合することにより配合
した請求項１，２または３記載の薬剤。5. Mixing ascorbyl gamma linolenic acid or ascorbyl dihomo gamma linolenic acid with an oil containing 5% by weight or more of gamma linolenic acid, dihomo gamma linolenic acid or eicosapentaenoic acid in the form of a free acid or triglyceride. The drug according to claim 1, 2 or 3, which is formulated by
たは化粧品もしくはスキンケア製品、または栄養補足物
を含む任意の種類の食品に使用するためのアスコルビル
ジホモガンマリノレン酸。6. Ascorbyl dihomogamma linolenic acid in its neat form and for use in therapy or in cosmetics or skin care products, or in any type of food product, including nutritional supplements.
の種類の食品に使用するためのアスコルビルガンマリノ
レン酸。7. Ascorbyl gamma linolenic acid for use therapeutically or in any type of food product containing nutritional supplements.
レー、エーロゾル、リポソームまたはその他の形態物に
配合したアスコルビルガンマリノレン酸またはアスコル
ビルジホモガンマリノレン酸。8. Ascorbyl gamma linolenic acid or ascorbyl dihomo gamma linolenic acid formulated in suspension, spray, aerosol, liposome or other form for release into the respiratory tract.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9403855A GB9403855D0 (en) | 1994-03-01 | 1994-03-01 | Fatty acid derivatives |
| GB94038551 | 1994-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07309753A true JPH07309753A (en) | 1995-11-28 |
Family
ID=10751060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7037258A Pending JPH07309753A (en) | 1994-03-01 | 1995-02-24 | Fatty acid derivative and medicine containing it |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5847000A (en) |
| EP (1) | EP0675120B1 (en) |
| JP (1) | JPH07309753A (en) |
| KR (1) | KR950031065A (en) |
| CN (1) | CN1111508A (en) |
| AT (1) | ATE208384T1 (en) |
| AU (1) | AU703651B2 (en) |
| CA (1) | CA2143603A1 (en) |
| DE (1) | DE69523654T2 (en) |
| DK (1) | DK0675120T3 (en) |
| ES (1) | ES2167401T3 (en) |
| FI (1) | FI950909A (en) |
| GB (1) | GB9403855D0 (en) |
| NO (1) | NO950784L (en) |
| NZ (1) | NZ270575A (en) |
| PT (1) | PT675120E (en) |
| SG (1) | SG50339A1 (en) |
| TW (1) | TW360537B (en) |
| ZA (1) | ZA951505B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| JP2014505679A (en) * | 2010-12-21 | 2014-03-06 | ネステク ソシエテ アノニム | Methods and compositions for prevention and treatment of osteoarthritis |
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| JP2017516823A (en) * | 2014-06-04 | 2017-06-22 | ディグニティ サイエンシス リミテッド | Pharmaceutical compositions containing DGLA and uses thereof |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| GB0111282D0 (en) * | 2001-05-09 | 2001-06-27 | Laxdale Ltd | Potentiation of therapeutic effects of fatty acids |
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| JP3847693B2 (en) * | 2002-09-30 | 2006-11-22 | シャープ株式会社 | Manufacturing method of semiconductor device |
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Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE639776C (en) * | 1934-06-12 | 1936-12-12 | Hoffmanni La Roche & Co Akt Ge | Process for the preparation of compounds of ascorbic acid |
| CH339632A (en) * | 1955-07-07 | 1959-07-15 | Uni Chemie Ag | Process for the preparation of compounds with vitamin C and F effects |
| BE639828A (en) * | 1962-11-14 | |||
| DE1231848B (en) * | 1965-04-15 | 1967-01-05 | Thomae Gmbh Dr K | Process for the production of stable tablets containing vitamin C |
| CH631451A5 (en) * | 1976-10-05 | 1982-08-13 | Univ Kansas State | METHOD FOR PRODUCING FATTY ACID ESTERS OF ASCORBIN ACID. |
| GB1580444A (en) * | 1976-11-04 | 1980-12-03 | Bio Oil Res | Pharmaceutical compositions |
| US4289702A (en) * | 1977-12-16 | 1981-09-15 | Pfizer Inc. | Preparation of erythorbic acid and ascorbis acid 6-fatty acid esters |
| IE49783B1 (en) * | 1979-05-18 | 1985-12-11 | Efamol Ltd | Pharmaceutical and dietary composition comprising epsilon-linolenic acids |
| IE53332B1 (en) * | 1980-03-14 | 1988-10-26 | Efamol Ltd | Pharmaceutical compositions |
| DE3366838D1 (en) * | 1982-03-01 | 1986-11-20 | Efamol Ltd | Pharmaceutical composition |
| AU1933383A (en) * | 1982-09-22 | 1984-03-29 | Sentrachem Limited | Composition of prostaglandins for prevention of cancer |
| GB8302708D0 (en) * | 1983-02-01 | 1983-03-02 | Efamol Ltd | Pharmaceutical and dietary composition |
| DE3308922A1 (en) * | 1983-03-12 | 1984-09-13 | Basf Ag, 6700 Ludwigshafen | METHOD FOR PRODUCING FATTY ACID ESTERS OF ASCORBIN ACID |
| JPS59199636A (en) * | 1983-04-26 | 1984-11-12 | Nippon Mejifuijitsukusu Kk | Radioactive diagnostic agent and production thereof |
| ATE55905T1 (en) * | 1984-03-07 | 1990-09-15 | Roshdy Ismail | MEANS FOR TREATMENT AND PROTECTION OF THE SKIN. |
| US4818521A (en) * | 1985-04-18 | 1989-04-04 | Sunstar Kabushiki Kaisha | Emulsion cosmetic stably containing vitamin C |
| US4792418A (en) * | 1985-08-14 | 1988-12-20 | Century Laboratories, Inc. | Method of extraction and purification of polyunsaturated fatty acids from natural sources |
| US4822898A (en) * | 1985-09-20 | 1989-04-18 | Sumitomo Chemical Company, Limited | Ascorbic acid or erythorbic acid derivatives |
| JPS6281307A (en) * | 1985-10-04 | 1987-04-14 | Kanebo Ltd | Skin cosmetic |
| JP2869650B2 (en) * | 1987-05-15 | 1999-03-10 | チッソ株式会社 | Optically active compound and method for producing the same |
| DK291588A (en) * | 1987-06-26 | 1988-12-27 | Hoffmann La Roche | METHOD FOR PREPARING ASCORBIC ACID ESTERS 6 |
| JPH0818963B2 (en) * | 1987-09-28 | 1996-02-28 | サンスター株式会社 | Whitening cosmetics |
| DE3820693A1 (en) * | 1988-06-18 | 1989-12-21 | Henkel Kgaa | TOPICAL COSMETIC AND PHARMACEUTICAL PREPARATIONS |
| US5591446A (en) * | 1989-04-04 | 1997-01-07 | Beiersdorf, A.G. | Methods and agents for the prophylaxis of atopy |
| DK0398484T3 (en) * | 1989-05-19 | 1995-07-24 | Hayashibara Biochem Lab | Alpha-Glycosyl-L-ascorbic acid, preparation and uses thereof |
| EP0401704B1 (en) * | 1989-06-03 | 1995-02-15 | Mitsubishi Rayon Co., Ltd | Process for the preparation of organic esters |
| JP2831395B2 (en) * | 1989-09-12 | 1998-12-02 | ハリマ化成株式会社 | Ascorbic acid ester |
| US5122536A (en) * | 1989-10-12 | 1992-06-16 | Perricone Nicholas V | Method for the topical treatment of psoriasis |
| US5574063A (en) * | 1989-10-12 | 1996-11-12 | Perricone; Nicholas V. | Method and compositions for topical application of ascorbic acid fatty acid esters for treatment and/or prevention of skin damage |
| GB9001121D0 (en) * | 1990-01-18 | 1990-03-21 | Efamol Holdings | Efa compositions and therapy |
| US5078989A (en) * | 1990-03-28 | 1992-01-07 | Sunstar K.K. | Skin whitening cosmetics |
| JPH05209968A (en) * | 1990-12-28 | 1993-08-20 | Hamamatsu Photonics Kk | Radiation detecting device |
| GB9111900D0 (en) * | 1991-06-03 | 1991-07-24 | Efamol Holdings | Fatty acid compositions |
| DE4133694C2 (en) * | 1991-10-11 | 1993-10-07 | Fresenius Ag | Use of an emulsion with polyunsaturated fatty acids for i.v. administration for the treatment of skin diseases |
| JPH05219970A (en) * | 1992-02-10 | 1993-08-31 | Mitsubishi Rayon Co Ltd | Production of organic acid ester |
| GB9213322D0 (en) * | 1992-06-23 | 1992-08-05 | Efamol Holdings | Antioxidant compositions |
| GB9217780D0 (en) * | 1992-08-21 | 1992-10-07 | Efamol Holdings | Fatty acid treatment |
| TW325997B (en) * | 1993-02-02 | 1998-02-01 | Senju Pharma Co | Pharmaceutical composition for preventing and treating retinal diseases |
| US5516793A (en) * | 1993-04-26 | 1996-05-14 | Avon Products, Inc. | Use of ascorbic acid to reduce irritation of topically applied active ingredients |
| CN1091591C (en) * | 1994-02-04 | 2002-10-02 | 利珀克尔集团公司 | Lipophilic carrier preparations |
| AU711482B2 (en) * | 1994-06-28 | 1999-10-14 | Scotia Holdings Plc | Compositions for treatment of diabetic complications |
-
1994
- 1994-03-01 GB GB9403855A patent/GB9403855D0/en active Pending
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1995
- 1995-02-22 AU AU13408/95A patent/AU703651B2/en not_active Ceased
- 1995-02-23 ZA ZA951505A patent/ZA951505B/en unknown
- 1995-02-24 JP JP7037258A patent/JPH07309753A/en active Pending
- 1995-02-27 NZ NZ270575A patent/NZ270575A/en unknown
- 1995-02-28 FI FI950909A patent/FI950909A/en not_active Application Discontinuation
- 1995-02-28 NO NO950784A patent/NO950784L/en not_active Application Discontinuation
- 1995-02-28 SG SG1995000051A patent/SG50339A1/en unknown
- 1995-02-28 CA CA002143603A patent/CA2143603A1/en not_active Abandoned
- 1995-03-01 DE DE69523654T patent/DE69523654T2/en not_active Expired - Fee Related
- 1995-03-01 AT AT95301316T patent/ATE208384T1/en not_active IP Right Cessation
- 1995-03-01 CN CN95102756A patent/CN1111508A/en active Pending
- 1995-03-01 PT PT95301316T patent/PT675120E/en unknown
- 1995-03-01 ES ES95301316T patent/ES2167401T3/en not_active Expired - Lifetime
- 1995-03-01 DK DK95301316T patent/DK0675120T3/en active
- 1995-03-01 EP EP95301316A patent/EP0675120B1/en not_active Expired - Lifetime
- 1995-03-02 KR KR1019950004287A patent/KR950031065A/en not_active Application Discontinuation
- 1995-03-30 TW TW084103055A patent/TW360537B/en active
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1997
- 1997-03-28 US US08/828,716 patent/US5847000A/en not_active Expired - Fee Related
-
1998
- 1998-03-02 US US09/034,029 patent/US6177470B1/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006524234A (en) * | 2003-04-21 | 2006-10-26 | タグラ バイオテクノロジーズ リミテッド | Stabilized derivatives of ascorbic acid |
| JP2006056795A (en) * | 2004-08-18 | 2006-03-02 | Suntory Ltd | Skin cosmetic and food and drink comprising 6-o-pufa ascorbic acid ester |
| JP2014505679A (en) * | 2010-12-21 | 2014-03-06 | ネステク ソシエテ アノニム | Methods and compositions for prevention and treatment of osteoarthritis |
| JP2014111621A (en) * | 2014-01-27 | 2014-06-19 | Suntory Holdings Ltd | Skin cosmetic and drink/food containing 6-o-pufa ascorbic acid ester |
| JP2017516823A (en) * | 2014-06-04 | 2017-06-22 | ディグニティ サイエンシス リミテッド | Pharmaceutical compositions containing DGLA and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA951505B (en) | 1995-12-08 |
| NO950784D0 (en) | 1995-02-28 |
| CA2143603A1 (en) | 1995-09-02 |
| TW360537B (en) | 1999-06-11 |
| ATE208384T1 (en) | 2001-11-15 |
| NO950784L (en) | 1995-09-04 |
| ES2167401T3 (en) | 2002-05-16 |
| GB9403855D0 (en) | 1994-04-20 |
| FI950909A0 (en) | 1995-02-28 |
| US5847000A (en) | 1998-12-08 |
| DK0675120T3 (en) | 2002-03-11 |
| KR950031065A (en) | 1995-12-18 |
| AU703651B2 (en) | 1999-04-01 |
| US6177470B1 (en) | 2001-01-23 |
| EP0675120A3 (en) | 1998-07-08 |
| AU1340895A (en) | 1995-09-07 |
| FI950909A (en) | 1995-09-02 |
| EP0675120A2 (en) | 1995-10-04 |
| DE69523654T2 (en) | 2002-08-01 |
| NZ270575A (en) | 1998-08-26 |
| DE69523654D1 (en) | 2001-12-13 |
| PT675120E (en) | 2002-04-29 |
| CN1111508A (en) | 1995-11-15 |
| SG50339A1 (en) | 1998-07-20 |
| EP0675120B1 (en) | 2001-11-07 |
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